A win in New York would also make Djokovic the first man since Rod Laver in 1969 to win a Calendar Grand Slam.
The world No.1 has been drawn in the same half as Alexander Zverev, the fourth seed and his recent Olympics conqueror, so if Murray is to make the final he could instead face last year’s runner-up.
Matteo Berrettini and Denis Shapovalov are also lurking in the opposite half of the draw as potential finals opponents, with the pair having made a maiden Grand Slam final and maiden Slam semi-final appearances respectively at Wimbledon last month.
Murray has only won the US Open once before when he defeated then-defending champion Djokovic 7-6(10) 7-5 2-6 3-6 6-2 to win his maiden Slam title.
However, the 34-year-old is now ranked much lower than he was in 2012, when he entered the tournament as the third seed.
The Brit has spent the last few years struggling with injuries, most notably undergoing hip resurfacing surgery in 2019, and has worked his way back up to world No 114.
He managed to defeat 24th seed Nikoloz Basilashvili and qualifier Oscar Otte at Wimbledon last month before falling to world No.10 Shapovalov in the third round.